Gastric cancer is one of the most common cancers worldwide. Epidemiologic and pathologic studies have demonstrated that gastric cancer development is a multi-step process. Intestinal metaplasia and dysplasia are considered to be important gastric premalignant lesions. The molecular nature of the development of these premalignant lesions remains largely unknown. In this application, we propose to use laser microdissection and cDNA microarrays to study the expression patterns associated with normal, intestinal metaplasia and dysplasia gastric epithelial cells. The genes identified from the study can be compared with the list of genes that are highly expressed in malignant gastric tissues we generated in our previous studies. The goal of the project is to identify and validate genes that are may be important for gastric tumorigenesis. In this application, we propose the following three aims: Aim 1: to profile gene expression patterns with intestinal metaplasia and dysplasia; Aim 2: To identify genes that are associated with gastric premalignant lesions and genes that are associated with gastric tumorigenesis; and 3: To validate the expression and study the cellular localization of the candidate genes. In summary, the proposed study of gene expression patterns associated with premalignant transformation in gastric epithelial cells will identify genes that are differentially expressed during different steps of the gastric tumorigenesis process. This exploratory R03 grant will set the stage for future studies, including clinical studies of markers for screening of high risk patients, and mechanistic studies of genes involved in gastric cancer development and progression.